CA2509202A1 - Fused heterocyclic derivatives as ppar modulators - Google Patents
Fused heterocyclic derivatives as ppar modulators Download PDFInfo
- Publication number
- CA2509202A1 CA2509202A1 CA002509202A CA2509202A CA2509202A1 CA 2509202 A1 CA2509202 A1 CA 2509202A1 CA 002509202 A CA002509202 A CA 002509202A CA 2509202 A CA2509202 A CA 2509202A CA 2509202 A1 CA2509202 A1 CA 2509202A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- phenyl
- group
- aryl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 101150014691 PPARA gene Proteins 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 232
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 116
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 44
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 43
- 229910020008 S(O) Inorganic materials 0.000 claims abstract description 36
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 36
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 17
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 17
- 150000003536 tetrazoles Chemical class 0.000 claims abstract description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 122
- 239000001257 hydrogen Substances 0.000 claims description 114
- 150000002431 hydrogen Chemical group 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 62
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 47
- -1 aryl-C0-4-alkyl Chemical group 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000004104 aryloxy group Chemical group 0.000 claims description 35
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 125000005466 alkylenyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 239000004480 active ingredient Substances 0.000 claims description 22
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
- 241000124008 Mammalia Species 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 18
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 18
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 18
- 125000002619 bicyclic group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 150000004677 hydrates Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 8
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 8
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 150000003857 carboxamides Chemical class 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 102000048124 delta Opioid Receptors Human genes 0.000 claims description 5
- 229960003424 phenylacetic acid Drugs 0.000 claims description 5
- 239000003279 phenylacetic acid Substances 0.000 claims description 5
- UMWZZLDNVUQPRY-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 UMWZZLDNVUQPRY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- QXMPETNONJQAMV-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 QXMPETNONJQAMV-UHFFFAOYSA-N 0.000 claims description 3
- NKTJHYBYKQVDLG-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7,8,9-hexahydrocycloocta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 NKTJHYBYKQVDLG-UHFFFAOYSA-N 0.000 claims description 3
- WPGUAIZCNYEENQ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-UHFFFAOYSA-N 0.000 claims description 3
- MLRJYOJSBPJMGJ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MLRJYOJSBPJMGJ-UHFFFAOYSA-N 0.000 claims description 3
- AJPCZXSCOFDKMF-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-UHFFFAOYSA-N 0.000 claims description 3
- MASRIAZPJQZFBO-KRWDZBQOSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-KRWDZBQOSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 102000005962 receptors Human genes 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- MOOIYJNTZBLQJB-UHFFFAOYSA-N 2-[2-methyl-4-[1-[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]ethylsulfanyl]phenoxy]acetic acid Chemical compound C=1C=CC=2SC(C=3C=CC(=CC=3)C(F)(F)F)=NC=2C=1C(C)SC1=CC=C(OCC(O)=O)C(C)=C1 MOOIYJNTZBLQJB-UHFFFAOYSA-N 0.000 claims description 2
- WPGUAIZCNYEENQ-INIZCTEOSA-N 2-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-INIZCTEOSA-N 0.000 claims description 2
- XSEIFFMZKVPKCQ-KRWDZBQOSA-N 2-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-KRWDZBQOSA-N 0.000 claims description 2
- WPGUAIZCNYEENQ-MRXNPFEDSA-N 2-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-MRXNPFEDSA-N 0.000 claims description 2
- MOMMQBFMXWNUCB-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(OCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MOMMQBFMXWNUCB-UHFFFAOYSA-N 0.000 claims description 2
- XSEIFFMZKVPKCQ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-UHFFFAOYSA-N 0.000 claims description 2
- MQFZYVYYQVKLOX-UHFFFAOYSA-N 2-[2-methyl-4-[[7-methyl-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=2N=C(C=3C=CC(=CC=3)C(F)(F)F)SC=2C(C)CCC1CSC1=CC=C(OCC(O)=O)C(C)=C1 MQFZYVYYQVKLOX-UHFFFAOYSA-N 0.000 claims description 2
- AYEMAHRIKLHTPJ-INIZCTEOSA-N 2-[3-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AYEMAHRIKLHTPJ-INIZCTEOSA-N 0.000 claims description 2
- AJPCZXSCOFDKMF-HNNXBMFYSA-N 2-[3-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-HNNXBMFYSA-N 0.000 claims description 2
- AYEMAHRIKLHTPJ-MRXNPFEDSA-N 2-[3-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AYEMAHRIKLHTPJ-MRXNPFEDSA-N 0.000 claims description 2
- AJPCZXSCOFDKMF-OAHLLOKOSA-N 2-[3-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-OAHLLOKOSA-N 0.000 claims description 2
- ISFGGMBEAJESIE-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 ISFGGMBEAJESIE-UHFFFAOYSA-N 0.000 claims description 2
- VRZRNMUGRLBYMH-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VRZRNMUGRLBYMH-UHFFFAOYSA-N 0.000 claims description 2
- CQIQSYRFMSPLGA-UHFFFAOYSA-N 3-[2-methyl-4-[1-[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]ethylsulfanyl]phenyl]propanoic acid Chemical compound C=1C=CC=2SC(C=3C=CC(=CC=3)C(F)(F)F)=NC=2C=1C(C)SC1=CC=C(CCC(O)=O)C(C)=C1 CQIQSYRFMSPLGA-UHFFFAOYSA-N 0.000 claims description 2
- GEWKLPAJUKPLJR-SFHVURJKSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GEWKLPAJUKPLJR-SFHVURJKSA-N 0.000 claims description 2
- VSMDKBVLWCUDSE-SFHVURJKSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VSMDKBVLWCUDSE-SFHVURJKSA-N 0.000 claims description 2
- GEWKLPAJUKPLJR-GOSISDBHSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GEWKLPAJUKPLJR-GOSISDBHSA-N 0.000 claims description 2
- AFPSGVLCIZLFNL-LJQANCHMSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AFPSGVLCIZLFNL-LJQANCHMSA-N 0.000 claims description 2
- MASRIAZPJQZFBO-QGZVFWFLSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-QGZVFWFLSA-N 0.000 claims description 2
- PXVZUEYBHCULQB-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 PXVZUEYBHCULQB-UHFFFAOYSA-N 0.000 claims description 2
- VSMDKBVLWCUDSE-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VSMDKBVLWCUDSE-UHFFFAOYSA-N 0.000 claims description 2
- NDPLSNYDLNHLSV-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 NDPLSNYDLNHLSV-UHFFFAOYSA-N 0.000 claims description 2
- AFPSGVLCIZLFNL-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AFPSGVLCIZLFNL-UHFFFAOYSA-N 0.000 claims description 2
- RJTQUAYEWRMUMM-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 RJTQUAYEWRMUMM-UHFFFAOYSA-N 0.000 claims description 2
- MASRIAZPJQZFBO-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-UHFFFAOYSA-N 0.000 claims description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 claims description 2
- 108010015181 PPAR delta Proteins 0.000 claims description 2
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 2
- PKCBADCPSHELDO-UHFFFAOYSA-N ethyl 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetate Chemical compound C1=C(C)C(OCC(=O)OCC)=CC=C1SCC1=CC=CC2=C1N=C(C=1C=CC(=CC=1)C(F)(F)F)S2 PKCBADCPSHELDO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 21
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 8
- LKTNJCONYPMERP-FQEVSTJZSA-N (2s)-2-methoxy-3-[4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](OC)C(O)=O)=CC=C1OCC1=CC=CC2=C1N=C(C=1C=CC(=CC=1)C(F)(F)F)S2 LKTNJCONYPMERP-FQEVSTJZSA-N 0.000 claims 1
- LSYQBJIIKXNEHU-UHFFFAOYSA-N 2-[2-ethyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-7-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(CC)=CC(SCC=2C=3SC(=NC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 LSYQBJIIKXNEHU-UHFFFAOYSA-N 0.000 claims 1
- IPBJYPMKHRCNDL-UHFFFAOYSA-N 2-[2-ethyl-4-[[2-[4-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(CC)=CC(SCC=2C=3N=C(NC=3N=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 IPBJYPMKHRCNDL-UHFFFAOYSA-N 0.000 claims 1
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- XSEIFFMZKVPKCQ-QGZVFWFLSA-N 2-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-QGZVFWFLSA-N 0.000 claims 1
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- XXTWNWQHEGVDMQ-UHFFFAOYSA-N methyl 2-(4-methoxy-2-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C=C1C XXTWNWQHEGVDMQ-UHFFFAOYSA-N 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
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- 231100000827 tissue damage Toxicity 0.000 description 1
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- 150000003626 triacylglycerols Chemical class 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- UDOZVPVDQKQJAP-UHFFFAOYSA-N trifluoroamine oxide Chemical compound [O-][N+](F)(F)F UDOZVPVDQKQJAP-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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US43854003P | 2003-01-06 | 2003-01-06 | |
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US60/438,541 | 2003-01-06 | ||
US60/438,540 | 2003-01-06 | ||
PCT/US2003/039120 WO2004063155A1 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as ppar modulators |
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CA2509202A1 true CA2509202A1 (en) | 2004-07-29 |
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US (2) | US7384965B2 (de) |
EP (1) | EP1585726A1 (de) |
JP (1) | JP2006516254A (de) |
AU (1) | AU2003296405A1 (de) |
CA (1) | CA2509202A1 (de) |
WO (1) | WO2004063155A1 (de) |
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WO2004063155A1 (en) * | 2003-01-06 | 2004-07-29 | Eli Lilly And Company | Fused heterocyclic derivatives as ppar modulators |
EP1706386A1 (de) | 2003-12-22 | 2006-10-04 | Eli Lilly And Company | Bicyclische derivate als ppar-modulatoren |
US7868033B2 (en) | 2004-05-20 | 2011-01-11 | Foldrx Pharmaceuticals, Inc. | Compounds, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
FR2879194B1 (fr) * | 2004-12-14 | 2007-01-19 | Galderma Res & Dev | Nouveaux composes bi-aromatiques modulateurs des recepteurs de type ppar, leur procede de preparation et leur utilisation dans des compositions cosmetiques ou pharmaceutiques |
DK1828177T3 (da) * | 2004-12-17 | 2008-11-17 | Lilly Co Eli | Hidtil ukendte MCH-receptorantagonister |
JP2007063225A (ja) * | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
AU2006287521A1 (en) * | 2005-09-07 | 2007-03-15 | Plexxikon, Inc. | PPARactive compounds |
AU2006322845A1 (en) * | 2005-12-07 | 2007-06-14 | Sepal Pharma Ltd. | Jasmonate derivatives, pharmaceutical compositions and methods of use thereof |
US9284274B2 (en) | 2005-12-07 | 2016-03-15 | Ramot At Tel-Aviv University Ltd. | Chemical derivatives of jasmonate, pharmaceutical compositions and methods of use thereof |
BRPI0706780A2 (pt) * | 2006-01-30 | 2011-04-05 | Irm Llc | compostos e composições como moduladores de ppar |
CA2647545C (en) * | 2006-04-03 | 2016-02-23 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Amide substituted indazole and benzotriazole derivatives as poly(adp-ribose)polymerase (parp) inhibitors |
PE20080188A1 (es) * | 2006-04-18 | 2008-03-10 | Janssen Pharmaceutica Nv | Derivados del acido benzoazepin-oxi-acetico como agonistas de ppar-delta usados para aumentar hdl-c, reducir ldl-c y reducir colesterol |
PE20080888A1 (es) | 2006-10-18 | 2008-08-26 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE LA ACIL-TRANSFERASA DE ACIL-CoA-DIACIL-GLICEROL 1 (DGAT1) |
PL2109608T3 (pl) * | 2007-01-10 | 2011-08-31 | Msd Italia Srl | Indazole podstawione grupą amidową jako inhibitory polimerazy poli(ADP-rybozy)-(PARP) |
JP5632612B2 (ja) * | 2007-12-05 | 2014-11-26 | あすか製薬株式会社 | ラクタム化合物又はその塩及びppar活性化剤 |
AU2008338963A1 (en) * | 2007-12-13 | 2009-06-25 | Sri International | PPAR-delta ligands and methods of their use |
GB0800035D0 (en) * | 2008-01-02 | 2008-02-13 | Glaxo Group Ltd | Compounds |
AR074760A1 (es) * | 2008-12-18 | 2011-02-09 | Metabolex Inc | Agonistas del receptor gpr120 y usos de los mismos en medicamentos para el tratamiento de diabetes y el sindrome metabolico. |
US9284252B2 (en) | 2009-06-09 | 2016-03-15 | Sepal Pharma Ltd. | Use of jasmonate ester derivatives for treating benign hyperproliferative skin disorders |
JP2013538215A (ja) | 2010-08-31 | 2013-10-10 | エスエヌユー アールアンドディービー ファウンデーション | PPARδアゴニストの胎児再プログラミング用途 |
WO2012081570A1 (ja) * | 2010-12-14 | 2012-06-21 | あすか製薬株式会社 | ラクタム化合物又はその塩及びppar活性化剤 |
KR101395146B1 (ko) | 2011-02-09 | 2014-05-16 | 부산대학교 산학협력단 | 피부미백, 항산화 및 ppar 활성을 갖는 신규 화합물 및 이의 의학적 용도 |
AR088377A1 (es) | 2011-10-20 | 2014-05-28 | Siena Biotech Spa | Proceso para la preparacion de 6-cloro-2,3,4,9-tetrahidro-1h-carbazol-1-carboxamida y compuestos intermedios de esta |
US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
TWI692469B (zh) * | 2012-11-09 | 2020-05-01 | 南韓商Lg化學股份有限公司 | Gpr40受體促效劑,製造該促效劑的方法以及含有該促效劑作爲活性劑的醫藥組成物 |
US9540362B2 (en) | 2013-02-20 | 2017-01-10 | Lg Life Sciences Ltd. | Sphingosine-1-phosphate receptor agonists, methods of preparing the same, and pharmaceutical compositions containing the same as an active agent |
BR112015022290B1 (pt) | 2013-03-14 | 2022-03-03 | Janssen Pharmaceutica Nv | Derivados de heterocíclicos benzo-fundidos, seu uso como agonistas de gpr120 e composição farmacêutica que os compreende |
AU2014241390B2 (en) | 2013-03-14 | 2018-04-12 | Janssen Pharmaceutica Nv | GPR120 agonists for the treatment of type II diabetes |
US9045454B2 (en) | 2013-03-14 | 2015-06-02 | Jansen Pharmaceutica Nv | Bicyclic pyrrole derivatives useful as agonists of GPR120 |
US9394285B2 (en) | 2013-03-15 | 2016-07-19 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
US9067898B1 (en) | 2014-03-07 | 2015-06-30 | Janssen Pharmaceutica Nv | Isothiazole derivatives as GPR120 agonists for the treatment of type II diabetes |
US8912227B1 (en) | 2014-03-07 | 2014-12-16 | Janssen Pharmaceutica Nv | Bicyclic pyrrole derivatives useful as agonists of GPR120 |
WO2016021706A1 (ja) * | 2014-08-08 | 2016-02-11 | カズマパートナーズ株式会社 | 縮合複素環化合物 |
TW201629033A (zh) | 2014-10-08 | 2016-08-16 | 健生藥品公司 | 作為治療第二型糖尿病之gpr40促效劑的經取代苯并噻吩基衍生物 |
JP2017531194A (ja) | 2014-10-16 | 2017-10-19 | 日東電工株式会社 | 呼気センサ器具 |
WO2017027309A1 (en) | 2015-08-12 | 2017-02-16 | Janssen Pharmaceutica Nv | Gpr40 agonists for the treatment of type ii diabetes |
WO2017027312A1 (en) | 2015-08-12 | 2017-02-16 | Janssen Pharmaceutica Nv | Gpr40 agonists for the treatment of type ii diabetes |
US9908873B2 (en) | 2015-08-12 | 2018-03-06 | Janssen Pharmaceutica Nv | GPR40 agonists for the treatment of type II diabetes |
WO2017180457A1 (en) | 2016-04-11 | 2017-10-19 | Janssen Pharmaceutica Nv | Gpr40 agonists in anti-diabetic drug combinations |
US10106553B2 (en) | 2016-04-11 | 2018-10-23 | Janssen Pharmaceutica Nv | Substituted benzothiophenyl derivatives as GPR40 agonists for the treatment of type II diabetes |
AR117472A1 (es) | 2018-12-21 | 2021-08-11 | Celgene Corp | Inhibidores de tienopiridina de ripk2 |
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US5859051A (en) * | 1996-02-02 | 1999-01-12 | Merck & Co., Inc. | Antidiabetic agents |
AU760163B2 (en) * | 1999-04-06 | 2003-05-08 | Sankyo Company Limited | Alpha-substituted carboxylic acid derivatives |
JP2002543065A (ja) | 1999-04-28 | 2002-12-17 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Ppap受容体リガンドとしてのトリアリール酸誘導体 |
GB9914977D0 (en) | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
CN1293042C (zh) * | 2002-02-07 | 2007-01-03 | 远藤仁 | 芳香族氨基酸衍生物及其药物组合物 |
WO2004063155A1 (en) * | 2003-01-06 | 2004-07-29 | Eli Lilly And Company | Fused heterocyclic derivatives as ppar modulators |
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US7384965B2 (en) | 2008-06-10 |
WO2004063155A1 (en) | 2004-07-29 |
AU2003296405A1 (en) | 2004-08-10 |
EP1585726A1 (de) | 2005-10-19 |
US20060205744A1 (en) | 2006-09-14 |
US20090054479A1 (en) | 2009-02-26 |
JP2006516254A (ja) | 2006-06-29 |
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